Sex differences in the inflammatory response of primary astrocytes to lipopolysaccharide

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Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response. Methods Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth) male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100 μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS) or with control medium. The mRNA levels of IL6, interferon-inducible protein 10 (IP10), TNFα, IL1β, Toll-like receptor 4 (TLR4), steroidogenic acute regulatory protein and translocator protein were assessed by quantitative real-time polymerase chain reaction. Statistical significance was assessed by unpaired t -test or by one-way analysis of variance followed by the Tukey post hoc test. Results The mRNA levels of IL6, TNFα and IL1β after LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicle-injected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicle-injected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to differences in the expression of the LPS receptor TLR4. In contrast, the different inflammatory response was associated with increased mRNA levels of translocator protein, a key steroidogenic regulator, in female astrocytes that were treated with LPS. Conclusions Male and female cortical astrocytes respond differentially to an inflammatory challenge and this may be predetermined by perinatal testosterone exposure.

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Published 01 January 2011
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SantosGalindoet al.Biology of Sex Differences2011,2:7 http://www.bsdjournal.com/content/2/1/7
R E S E A R C H
Open Access
Sex differences in the inflammatory response primary astrocytes to lipopolysaccharide * María SantosGalindo, Estefanía AcazFonseca, María J Bellini and Luis M GarciaSegura
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Abstract Background:Numerous neurological and psychiatric disorders show sex differences in incidence, age of onset, symptomatology or outcome. Astrocytes, one of the glial cell types of the brain, show sex differences in number, differentiation and function. Since astrocytes are involved in the response of neural tissue to injury and inflammation, these cells may participate in the generation of sex differences in the response of the brain to pathological insults. To explore this hypothesis, we have examined whether male and female astrocytes show a different response to an inflammatory challenge and whether perinatal testosterone influences this response. Methods:Cortical astrocyte cultures were prepared from postnatal day 1 (one day after birth) male or female CD1 mice pups. In addition, cortical astrocyte cultures were also prepared from female pups that were injected at birth with 100μg of testosterone propionate or vehicle. Cultures were treated for 5 hours with medium containing lipopolysaccharide (LPS) or with control medium. The mRNA levels of IL6, interferoninducible protein 10 (IP10), TNFa, IL1b, Tolllike receptor 4 (TLR4), steroidogenic acute regulatory protein and translocator protein were assessed by quantitative realtime polymerase chain reaction. Statistical significance was assessed by unpairedttest or by oneway analysis of variance followed by the Tukeypost hoctest. Results:The mRNA levels of IL6, TNFaand IL1bafter LPS treatment were significantly higher in astrocytes derived from male or androgenized females compared to astrocytes derived from control or vehicleinjected females. In contrast, IP10 mRNA levels after LPS treatment were higher in astrocytes derived from control or vehicleinjected females than in those obtained from males or androgenized females. The different response of male and female astrocytes to LPS was due neither to differences in the basal expression of the inflammatory molecules nor to differences in the expression of the LPS receptor TLR4. In contrast, the different inflammatory response was associated with increased mRNA levels of translocator protein, a key steroidogenic regulator, in female astrocytes that were treated with LPS. Conclusions:Male and female cortical astrocytes respond differentially to an inflammatory challenge and this may be predetermined by perinatal testosterone exposure. Keywords:IFNinducible protein 10, IL1β, IL6, steroidogenic acute regulatory protein, testosterone, Tolllike receptor 4, translocator protein 18 kDa, TNFα
Background Astrocytes, one of the glial cell types of the central nervous system (CNS), are involved in a variety of functions under physiological conditions, including the control of brain blood flow and neuronal metabolism [1,2]. In addition, astrocytes regulate extracellular potassium levels and neuronal excitability and, by means of astrocyteastrocyte and astrocyteneuron communication, participate in the
* Correspondence: lmgs@cajal.csic.es Instituto Cajal, CSIC, Avenida Doctor Arce 37, E28002 Madrid, Spain
regulation of synaptic transmission, synaptic plasticity and information processing in the CNS [3,4]. Astrocytes also play an important role under pathological conditions. Together with microglia, these cells participate in the local inflammatory response of the CNS, releasing a variety of inflammatory mediators, including cytokines, such as IL6, TNFaand IL1b, and chemokines, such as IFNinducible protein 10 (IP10) [57]. Astrocytes also express Tolllike receptor 4 (TLR4), which mediates the inflammatory actions of lipopolysaccharide (LPS) in these cells [812].
© 2011 SantosGalindo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.